Document Detail


Nifedipine, a calcium-channel blocker, attenuated glucose intolerance and white adipose tissue dysfunction in type 2 diabetic KK-A(y) mice.
MedLine Citation:
PMID:  20847723     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: To explore the metabolic actions of nifedipine on diabetes, we examined glucose intolerance and white adipose tissue changes in type 2 diabetic KK-A(y) mice.
METHODS: Male KK-A(y) mice were treated with nifedipine (1.5 mg/kg/day in lab chow) for 5 weeks, which did not affect blood pressure or feeding of KK-A(y) mice.
RESULTS: After treatment with nifedipine, body weight tended to decrease and the weight of white adipose tissue was reduced. Without food restriction, nifedipine decreased plasma insulin level, while plasma glucose level tended to decrease. In oral glucose tolerance test, nifedipine suppressed the increase in glucose level after a glucose load without affecting plasma insulin concentration. Nifedipine also improved the result of insulin tolerance test. In white adipose tissue, nifedipine increased adipocyte number and the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and adipocyte fatty acid-binding protein related to adipocyte differentiation. In addition, expression of adiponectin, insulin receptor, insulin receptor substrate-1, and glucose transporter type-4 was also increased by nifedipine. Nifedipine also increased the expression of NO synthase in white adipose tissue. Nifedipine did not affect expression of angiotensin II type 1 (AT₁) and type 2 (AT₂) receptors in white adipose tissue. Such changes in white adipose tissue were apparent in retroperitoneal adipose tissue. Nifedipine did not change the expression of angiotensin receptors, renin receptor, and angiotensinogen in white adipose tissue. Moreover, nifedipine attenuated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and increased superoxide dismutase (SOD) activity in white adipose tissue.
CONCLUSION: These results suggest that nifedipine can enhance insulin sensitivity and reduce white adipose tissue, possibly related to stimulation of adipocyte differentiation.
Authors:
Masaru Iwai; Harumi Kanno; Shinji Inaba; Izumi Senba; Hisako Sone; Hirotomo Nakaoka; Masatsugu Horiuchi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-16
Journal Detail:
Title:  American journal of hypertension     Volume:  24     ISSN:  1941-7225     ISO Abbreviation:  Am. J. Hypertens.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-20     Completed Date:  2011-05-03     Revised Date:  2012-04-09    
Medline Journal Info:
Nlm Unique ID:  8803676     Medline TA:  Am J Hypertens     Country:  United States    
Other Details:
Languages:  eng     Pagination:  169-74     Citation Subset:  IM    
Affiliation:
Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adipocytes / drug effects*,  metabolism
Adipogenesis / drug effects
Adiponectin / metabolism
Adipose Tissue, White / drug effects*,  metabolism,  physiopathology
Animals
Blood Glucose / drug effects*,  metabolism
Calcium Channel Blockers / pharmacology*
Diabetes Mellitus, Type 2 / drug therapy*,  metabolism,  physiopathology
Disease Models, Animal
Fatty Acid-Binding Proteins / metabolism
Glucose Tolerance Test
Glucose Transporter Type 4 / metabolism
Insulin / blood
Insulin Receptor Substrate Proteins / metabolism
Insulin Resistance*
Male
Mice
Mice, Inbred Strains
NADPH Oxidase / metabolism
Nifedipine / pharmacology*
Nitric Oxide Synthase / metabolism
Oxidative Stress / drug effects
PPAR gamma / metabolism
Receptors, Angiotensin / metabolism
Superoxide Dismutase / metabolism
Time Factors
Weight Loss
Chemical
Reg. No./Substance:
0/Adiponectin; 0/Adipoq protein, mouse; 0/Blood Glucose; 0/Calcium Channel Blockers; 0/Fabp4 protein, mouse; 0/Fatty Acid-Binding Proteins; 0/Glucose Transporter Type 4; 0/Insulin; 0/Insulin Receptor Substrate Proteins; 0/Irs1 protein, mouse; 0/PPAR gamma; 0/Receptors, Angiotensin; 0/Slc2a4 protein, mouse; 21829-25-4/Nifedipine; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.15.1.1/Superoxide Dismutase; EC 1.6.3.1/NADPH Oxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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